Association of Acid-Base Balance in the Renal Proximal Tubule and Blood Pressure Alterations: Potential Role of Local Mediators

Isoform 3 of the Na+/H+ exchanger (NHE3) is responsible for the majority of the reabsorption of NaCl, NaHCO3, and, consequently, water in the renal proximal tubule. As such, this transporter plays an essential role in acid-base balance and extracellular fluid volume homeostasis and determining systemic arterial blood pressure levels. NHE3 activity is modulated by a number of mechanisms, including the redistribution of the transporter between the body of the microvilli (where NHE3 is active) and the base of the microvilli (where NHE3 is less active). Although the physiological, pathophysiological, and pharmacological importance of the subcellular distribution of NHE3 has been well established, the exact mechanism whereby NHE3 is translocated along microvilli microdomains of the proximal tubule apical membrane is unknown. Nonmuscle myosin IIA and unconventional myosin VI move cargoes in anterograde and retrograde directions, respectively, and are known to redistribute along with NHE3 in the proximal tubule in response to a variety of natriuretic and antinatriuretic stimuli, including stimulation or inhibition of the renin-angiotensin system, high dietary Na+ intake, and high blood pressure. Therefore, this review aims to discuss the current evidence that suggests a potential role of myosin IIA and myosin VI in mediating the subcellular distribution of NHE3 along the kidney proximal tubule microvilli and their possible contribution in modifying NHE3-mediated Na+ reabsorption under both physiological and pathophysiological conditions.

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Role of organic anions in renal response to dietary acid and base loads

AJP Renal Physiology ◽

10.1152/ajprenal.1989.257.2.f170 ◽

1989 ◽

Vol 257 (2) ◽

pp. F170-F176 ◽

Cited By ~ 11

Author(s):

J. C. Brown ◽

R. K. Packer ◽

M. A. Knepper

Keyword(s):

Organic Anion ◽

Organic Anions ◽

Acid Excretion ◽

Acid Base Balance ◽

Acid Base ◽

Urine Ph ◽

Renal Response ◽

Base Balance ◽

Net Acid Excretion

Bicarbonate is formed when organic anions are oxidized systemically. Therefore, changes in organic anion excretion can affect systemic acid-base balance. To assess the role of organic anions in urinary acid-base excretion, we measured urinary excretion in control rats, NaHCO3-loaded rats, and NH4Cl-loaded rats. Total organic anions were measured by the titration method of Van Slyke. As expected, NaHCO3 loading increased urine pH and decreased net acid excretion (NH4+ + titratable acid - HCO3-), whereas NH4Cl loading had the opposite effect. Organic anion excretion was increased in response to NaHCO3 loading and decreased in response to NH4Cl loading. We quantified the overall effect of organic ion plus inorganic buffer ion excretion on acid-base balance. The amounts of organic anions excreted by all animals in this study were greater than the amounts of NH4+, HCO3-, or titratable acidity excreted. In addition, in response to acid and alkali loading, changes in urinary organic anion excretion were 40-50% as large as changes in net acid excretion. We conclude that, in rats, regulation of organic anion excretion can contribute importantly to the overall renal response to acid-base disturbances.

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Commentary to accompany the paper entitled ‘Nutritional disturbance in acid–base balance and osteoporosis: a hypothesis that disregards the essential homeostatic role of the kidney’, by Jean-Philippe Bonjour

British Journal Of Nutrition ◽

10.1017/s0007114513001499 ◽

2013 ◽

Vol 110 (11) ◽

pp. 1935-1937 ◽

Cited By ~ 1

Author(s):

Lynda A. Frassetto ◽

Anthony Sebastian

Keyword(s):

Acid Base Balance ◽

Acid Base ◽

Nutritional Disturbance ◽

Base Balance

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Intestinal base excretion in the seawater-adapted rainbow trout: a role in acid-base balance?

Journal of Experimental Biology ◽

10.1242/jeb.199.10.2331 ◽

1996 ◽

Vol 199 (10) ◽

pp. 2331-2343 ◽

Cited By ~ 17

Author(s):

R Wilson ◽

K Gilmour ◽

R Henry ◽

C Wood

Keyword(s):

Rainbow Trout ◽

Potential Role ◽

Excretion Rate ◽

Anterior Region ◽

Acid Base Balance ◽

Acid Base ◽

Opsanus Beta ◽

Base Balance ◽

High Fluid

A potential role for the intestine of seawater-adapted teleosts in acidbase regulation was investigated following earlier reports of highly alkaline rectal fluids in the gulf toadfish Opsanus beta. Rectal samples taken from starved seawater-adapted rainbow trout had a high fluid pH (8.90±0.03; mean ± s.e.m., N=13) and base (HCO3-+2CO32-) content of 157±26 mequiv kg-1 (N=11). In trout fitted with rectal catheters, rectal fluid was voided at a rate of 0.47±0.11 ml kg-1 h-1 (N=8), giving a net base excretion rate of 114±15 µequiv kg-1 h-1 (N=7). Drinking rates averaged 3.12±0.48 ml kg-1 h-1 (N=8), and accounted for only 6 % of the base excreted via the intestine, indicating substantial net transport of endogenously derived base into the intestine. Rectally excreted base was approximately balanced by an equivalent efflux of net acid from non-rectal sources (possibly as NH4+ excretion via the gills). Samples taken from four sites along the intestine revealed that the most anterior region (the pyloric intestine) was responsible for the majority of HCO3-+2CO32- accumulation. The pyloric intestine was subsequently perfused in situ to investigate possible mechanisms of base secretion. Net base fluxes were found to be dependent on luminal Cl-, 76 % stimulated by amiloride, 20 % inhibited by 10(-4) mol l-1 acetazolamide, but unaffected by either 10(-4) mol l-1 SITS or 2x10(-5) mol l-1 DIDS. This suggests that the mechanism of base secretion within the pyloric intestine may involve a Cl-/HCO3--ATPase. It is speculated that intestinal base secretion may play a role in facilitating osmoregulation of seawater-adapted teleosts.

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